The predictive value of systemic immune-inflammatory markers before and after treatment for pathological complete response in patients undergoing neoadjuvant therapy for breast cancer: a retrospective study of 1994 patients.

PURPOSE: Systemic immune-inflammatory markers have a certain predictive role in pathological complete response (pCR) after neoadjuvant treatment (NAT) in breast cancer. However, there is a lack of research exploring the predictive value of markers after treatment. METHODS: This retrospective study collected data from 1994 breast cancer patients who underwent NAT. Relevant clinical and pathological characteristics were included, and pre- and post-treatment complete blood cell counts were evaluated to calculate four systemic immune-inflammatory markers: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII). The optimal cutoff values for these markers were determined using ROC curves, and patients were classified into high-value and low-value groups based on these cutoff values. Univariate and multivariate logistic regression analyses were conducted to analyze factors influencing pCR. The factors with independent predictive value were used to construct a nomogram. RESULTS: After NAT, 383 (19.2%) patients achieved pCR. The area under the ROC curve is generally larger for post-treatment markers compared to pre-treatment markers. Pre-treatment NLR and PLR, as well as post-treatment LMR and SII, were identified as independent predictive factors for pCR, along with Ki-67, clinical tumor stage, clinical lymph node stage, molecular subtype, and clinical response. Higher pre-NLR (OR = 1.320; 95% CI 1.016-1.716; P = 0.038), pre-PLR (OR = 1.474; 95% CI 1.058-2.052; P = 0.022), post-LMR (OR = 1.532; 95% CI 1.175-1.996; P = 0.002), and lower post-SII (OR = 0.596; 95% CI 0.429-0.827; P = 0.002) are associated with a higher likelihood of achieving pCR. The established nomogram had a good predictive performance with an area under the ROC curve of 0.754 (95% CI 0.674-0.835). CONCLUSION: Both pre- and post-treatment systemic immune-inflammatory markers have a significant predictive role in achieving pCR after NAT in breast cancer patients. Indeed, it is possible that post-treatment markers have stronger predictive ability compared to pre-treatment markers.

SMEK1 promotes lung adenocarcinoma proliferation and invasion by activating Wnt/ß-catenin signaling pathway.

PURPOSE: SMEK1, also known as PP4R3α, the regulatory subunit 3α of serine and threonine phosphatase PP4, participates in diversely critical biological processes such as the integration of centromere, deacetylation of histones, asymmetric divisions of neuroblast, and other crucial cellular activities. SMEK1 was formerly reported to play a part in carcinogenesis. This study aims to reveal the role of SMEK1 in lung adenocarcinoma and the underlying molecular mechanism. METHODS: Using immunohistochemical (IHC) staining, the protein level of SMEK1 in lung adenocarcinoma and adjacent non-tumor tissue was detected. The functional role of SMEK1 in cell proliferation and invasion was explored using cell counting kit-8 and Transwell assay, respectively. Xenograft tumor experiment was used to investigate the effect of SMEK1 on tumor growth in vivo. The alteration of Wnt/ß-catenin signaling pathway was detected by Western blotting, quantitative PCR, and dual-luciferase reporter assays. RESULTS: SMEK1 was highly expressed at the protein level in lung adenocarcinoma compared to the adjacent non-tumor tissue. In vitro, suppression of SMEK1 significantly decreased the proliferation, migration, and invasion of lung adenocarcinoma cell lines, while overexpression of SMEK1 enhanced above abilities. The xenograft model demonstrated that down-regulation of SMEK1 significantly inhibited tumor growth in vivo. In addition, we found that SMEK1 could positively regulate Wnt/ß-catenin signaling in lung adenocarcinoma cell lines. CONCLUSIONS: SMEK1 exerts a cancer-promoting effect in lung adenocarcinoma by activating Wnt/ß-catenin signaling.

B3 Transcription Factors Determine Iron Distribution and FERRITIN Gene Expression in Embryo but Do Not Control Total Seed Iron Content.

Iron is an essential micronutrient for humans and other organisms. Its deficiency is one of the leading causes of anemia worldwide. The world health organization has proposed that an alternative to increasing iron content in food is through crop biofortification. One of the most consumed part of crops is the seed, however, little is known about how iron accumulation in seed occurs and how it is regulated. B3 transcription factors play a critical role in the accumulation of storage compounds such as proteins and lipids. Their role in seed maturation has been well characterized. However, their relevance in accumulation and distribution of micronutrients like iron remains unknown. In Arabidopsis thaliana and other plant models, three master regulators belonging to the B3 transcription factors family have been identified: FUSCA3 (FUS3), LEAFY COTYLEDON2 (LEC2), and ABSCISIC ACID INSENSITIVE 3 (ABI3). In this work, we studied how seed iron homeostasis is affected in B3 transcription factors mutants using histological and molecular approaches. We determined that iron distribution is modified in abi3, lec2, and fus3 embryo mutants. For abi3-6 and fus3-3 mutant embryos, iron was less accumulated in vacuoles of cells surrounding provasculature compared with wild type embryos. lec2-1 embryos showed no difference in the pattern of iron distribution in hypocotyl, but a dramatic decrease of iron was observed in cotyledons. Interestingly, for the three mutant genotypes, total iron content in dry mutant seeds showed no difference compared to wild type. At the molecular level, we showed that genes encoding the iron storage ferritins proteins are misregulated in mutant seeds. Altogether our results support a role of the B3 transcription factors ABI3, LEC2, and FUS3 in maintaining iron homeostasis in Arabidopsis embryos.

Evaluation of immune efficacy of recombinant PRRSV vectored vaccine rPRRSV-E2 in piglets with maternal derived antibodies.

Currently live attenuated porcine reproductive and respiratory syndrome (PRRS) and classical swine fever (CSF) vaccines are widely used in Chinese swine herds. However, the mutual effects of vaccination procedures and severe stress caused by successive vaccinations harm piglets and make it difficult to stimulate robust and effective immune responses. In our previous study, a recombinant PRRS virus (PRRSV) vectored vaccine candidate rPRRSV-E2, which expresses CSF virus (CSFV) E2 protein, has been demonstrated being able to protect piglets against lethal challenge of highly-pathogenic (HP)-PRRSV and CSFV. In this study, we determine whether preexisting maternally derived antibodies (MDA) interfere with the immune efficacy of rPRRSV-E2. 8 experimental groups of piglets, with or without PRRSV MDAs or CSFV MDAs were immunized with a single dose of 105 TCID50 rPRRSV-E2 or DMEM and challenged with HP-PRRSV or CSFV. Clinical characteristics, PRRSV- or CSFV-specific antibodies, viremia and pathological changes were monitored, examined and analyzed. The results showed that rPRRSV-E2-vaccinated piglets, either with or without MDAs directed against PRRSV or CSFV were completely protected from the lethal challenge of HP-PRRSV or CSFV. These results demonstrate that the MDAs do not interfere with the immune efficacy of rPRRSV-E2, which indicates that rPRRSV-E2 could have great significance in the effective prevention and control of HP-PRRSV and CSFV.

Musculoskeletal computational analysis on muscle mechanical characteristics of drivers' lumbar vertebras and legs in different sitting postures.

Using computer-aided engineering (CAE) in the concept design stage of automobiles has become a hotspot in human factor engineering research. Based on human musculoskeletal biomechanical computational software, a seated human-body musculoskeletal model was built to describe the natural sitting posture of a driver. The interaction between the driver and car in various combinations of seat-pan/back-rest inclination angles was analyzed using an inverse-dynamics approach. In order to find out the "most comfortable" driving posture of the seat-pan/back-rest, the effect of seat-pan/back-rest inclination angles on the muscle activity degree, and the intradiscal L4-L5 compression force were investigated. The results showed that a much larger back-rest inclination angle, approximately 15°, and a slight backward seat-pan, about 7°, may relieve muscle fatigue and provide more comfort while driving. Subsequently, according to the findings above, a preliminary driving-comfort function was constructed.

MALAT1 is involved in type I IFNs-mediated systemic lupus erythematosus by up-regulating OAS2, OAS3, and OASL.

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with an aberrant activation of immune cells partly due to the dysfunction of cytokines such as type I interferons (IFNs). Long non-coding RNA MALAT1 has been found to play a pathogenic role in SLE; however, the underlying mechanisms are still poorly understood. Bioinformatics analysis showed the up-regulation of type I IFN downstream effectors OAS2, OAS3, and OASL (OAS-like) in CD4+ T cells, CD19+ B cells, and CD33+ myeloid cells in patients with active SLE compared to healthy participants. In this study, peripheral blood mononuclear cells (PBMCs), CD19+ B, and CD4+ T cells were isolated from active SLE patients and healthy participants. PCR was performed to quantify MALAT1, OAS2, OAS3, and OASL expression in immune cells. MALAT1, OAS2, OAS3, and OASL were knocked down in CD4+ T cells to investigate the regulatory effect of MALAT1 on the effectors and their involvement in type I IFNs-mediated inflammation. Results showed higher OAS2, OAS3, and OASL expression in active SLE patients. MALAT1 expression was positively correlated to OAS2, OAS3, and OASL expression in CD19+ B or CD4+ T cells. MALAT1 knockdown decreased OAS2, OAS3, and OASL expression. Treatment with IFN-α-2a increased the expression of TNF-α, IL-1ß, and IFN-α in CD4+ T cells. However, knockdown of MALAT1, OAS2, OAS3, and OASL alone inhibited the effect of IFN-α-2a on TNF-α and IL-1ß. This study suggested the involvement of MALAT1 in type I IFNs-mediated SLE by up-regulating OAS2, OAS3, and OASL.

MALAT1 is involved in type I IFNs-mediated systemic lupus erythematosus by up-regulating OAS2, OAS3, and OASL

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with an aberrant activation of immune cells partly due to the dysfunction of cytokines such as type I interferons (IFNs). Long non-coding RNA MALAT1 has been found to play a pathogenic role in SLE; however, the underlying mechanisms are still poorly understood. Bioinformatics analysis showed the up-regulation of type I IFN downstream effectors OAS2, OAS3, and OASL (OAS-like) in CD4+ T cells, CD19+ B cells, and CD33+ myeloid cells in patients with active SLE compared to healthy participants. In this study, peripheral blood mononuclear cells (PBMCs), CD19+ B, and CD4+ T cells were isolated from active SLE patients and healthy participants. PCR was performed to quantify MALAT1, OAS2, OAS3, and OASL expression in immune cells. MALAT1, OAS2, OAS3, and OASL were knocked down in CD4+ T cells to investigate the regulatory effect of MALAT1 on the effectors and their involvement in type I IFNs-mediated inflammation. Results showed higher OAS2, OAS3, and OASL expression in active SLE patients. MALAT1 expression was positively correlated to OAS2, OAS3, and OASL expression in CD19+ B or CD4+ T cells. MALAT1 knockdown decreased OAS2, OAS3, and OASL expression. Treatment with IFN-α-2a increased the expression of TNF-α, IL-1β, and IFN-α in CD4+ T cells. However, knockdown of MALAT1, OAS2, OAS3, and OASL alone inhibited the effect of IFN-α-2a on TNF-α and IL-1β. This study suggested the involvement of MALAT1 in type I IFNs-mediated SLE by up-regulating OAS2, OAS3, and OASL.

Musculoskeletal computational analysis on muscle mechanical characteristics of drivers lumbar vertebras and legs in different sitting postures

SUMMARY Using computer-aided engineering (CAE) in the concept design stage of automobiles has become a hotspot in human factor engineering research. Based on human musculoskeletal biomechanical computational software, a seated human-body musculoskeletal model was built to describe the natural sitting posture of a driver. The interaction between the driver and car in various combinations of seat-pan/back-rest inclination angles was analyzed using an inverse-dynamics approach. In order to find out the "most comfortable" driving posture of the seat-pan/back-rest, the effect of seat-pan/back-rest inclination angles on the muscle activity degree, and the intradiscal L4-L5 compression force were investigated. The results showed that a much larger back-rest inclination angle, approximately 15°, and a slight backward seat-pan, about 7°, may relieve muscle fatigue and provide more comfort while driving. Subsequently, according to the findings above, a preliminary driving-comfort function was constructed.

RESUMO O uso de engenharia assistida por computador (CAE) na fase de projeto do conceito do automóvel tornou-se um ponto de acesso na pesquisa de fatores humanos. Com base no software computacional biomecânico musculoesquelético humano, foi construído um modelo musculoesquelético sentado para descrever a postura sentada natural de um condutor. A interação entre um motorista e um carro em várias combinações de ângulos de inclinação do assento-pan/encosto foi analisada usando uma abordagem dinâmica do verso. A fim de descobrir a postura de condução "mais confortável" do assento-pan/encosto, o efeito dos ângulos de inclinação do assento-pan/dorso sobre o grau de atividade muscular e a força de compressão intradiscal L4-L5 foi investigado. Os resultados mostraram que um ângulo de inclinação para trás muito maior, aproximadamente 15°, e um ligeiro assento-pan para trás, cerca de 7°, pode aliviar a fadiga muscular e levar a dirigir em uma posição confortável. Posteriormente, de acordo com as conclusões acima expostas, foi construída uma função preliminar de conforto ao dirigir.

The measurement of dorsal radial tilt by x-ray and computed tomography.

OBJECTIVE: We conducted this study to define and measure the dorsal radial tilt, and to guide the reduction of distal radius fractures and the pre-bending of steel plates used in surgery. METHODS: The dorsal radial tilt was measured using both computed tomography (CT) and x-ray from both left and right side. The differences and correlations of the data measured by those two methods and from two sides were analyzed. RESULTS: The tilts measured by x-ray were significantly bigger than those measured by CT from the left side (t=55.51, p < 0.01) and from the right side (t=49.81, p < 0.01). The tilts measured by those two methods from the left and right sides were correlated (r=0.85, p < 0.01; r=0.81, p < 0.01). The dorsal radial tilts measured from the left side were not significantly different from those measured from the right side by CT (t=1.49, p > 0.05) and by x-ray (t=1.51, p > 0.05). The dorsal radial tilts measured from the left side by CT were significantly different from those measured from the right side by x-ray (t=43.07, p < 0.01), and these two sets of data were correlated (r=0.71, p < 0.01). The dorsal radial tilts measured from the left side by x-ray was significantly different from that measured from right side by CT (t=40.43, p < 0.01), and those two sets of data were also correlated (r=0.75, p < 0.01). CONCLUSIONS: The dorsal radial tilts measured from one side by one method can be used to estimate the tilts measured from the other side / the same side by the same method / the other method.

The measurement of dorsal radial tilt by x-ray and computed tomography

SUMMARY OBJECTIVE: We conducted this study to define and measure the dorsal radial tilt, and to guide the reduction of distal radius fractures and the pre-bending of steel plates used in surgery. METHODS: The dorsal radial tilt was measured using both computed tomography (CT) and x-ray from both left and right side. The differences and correlations of the data measured by those two methods and from two sides were analyzed. RESULTS: The tilts measured by x-ray were significantly bigger than those measured by CT from the left side (t=55.51, p < 0.01) and from the right side (t=49.81, p < 0.01). The tilts measured by those two methods from the left and right sides were correlated (r=0.85, p < 0.01; r=0.81, p < 0.01). The dorsal radial tilts measured from the left side were not significantly different from those measured from the right side by CT (t=1.49, p > 0.05) and by x-ray (t=1.51, p > 0.05). The dorsal radial tilts measured from the left side by CT were significantly different from those measured from the right side by x-ray (t=43.07, p < 0.01), and these two sets of data were correlated (r=0.71, p < 0.01). The dorsal radial tilts measured from the left side by x-ray was significantly different from that measured from right side by CT (t=40.43, p < 0.01), and those two sets of data were also correlated (r=0.75, p < 0.01). Conclusions: The dorsal radial tilts measured from one side by one method can be used to estimate the tilts measured from the other side / the same side by the same method / the other method.

RESUMO OBJETIVO: Realizamos este estudo para definir e medir a inclinação radial dorsal, e para orientar a redução das fraturas do raio distal e a pré-flexão das chapas de aço utilizadas na cirurgia. MÉTODOS: A inclinação radial dorsal foi medida usando tomografia computadorizada (TC) e raios X dos lados esquerdo e direito. As diferenças e correlações dos dados medidos por esses dois métodos e de dois lados foram analisadas. RESULTADOS: As inclinações medidas por raios X foram significativamente maiores que as medidas pela TC do lado esquerdo (t=55,51, p<0,01) e do lado direito (t=49,81, p<0,01). As inclinações medidas por esses dois métodos dos lados esquerdo e direito foram correlacionadas (r=0,85, p<0,01; r=0,81, p<0,01). As inclinações radiais dorsais medidas a partir do lado esquerdo não foram significativamente diferentes das medidas do lado direito por CT (t=1,49, p>0,05) e por raios X (t=1,51, p>0,05). As inclinações radiais dorsais medidas a partir do lado esquerdo por TC foram significativamente diferentes das medidas a partir do lado direito por raios X (t=43,07, p<0,01), e esses dois conjuntos de dados foram correlacionados (r=0,71, p<0,01). As inclinações radiais dorsais medidas a partir do lado esquerdo por raios X foram significativamente diferentes das medidas do lado direito por CT (t=40,43, p<0,01), e esses dois conjuntos de dados também foram correlacionados (r=0,75, p<0,01). CONCLUSÕES: As inclinações radiais dorsais medidas de um lado por um método podem ser usadas para estimar as inclinações medidas do outro lado/o mesmo lado pelo mesmo método/o outro método.

Long-term prognosis and risk heterogeneity of heart failure complicating acute myocardial infarction.

The Killip classification of acute heart failure was developed decades ago to predict short-term mortality in patients with acute myocardial infarction (AMI). The aim of this study was to determine the long-term prognosis of acute heart failure graded according to the Killip classification in 15,235 unselected patients hospitalized for AMI from 2000 to 2005. Vital status for each patient was ascertained, through to March 1, 2012, from linkage with national death records. A stepwise gradient in the adjusted hazard ratio (HR) for 12-year mortality was observed with increasing Killip class: class I (n = 10,123), HR 1.00 (reference group); class II (n = 2,913), HR 1.13 (95% confidence interval [CI] 1.06 to 1.21); class III (n = 1,217) HR 1.49 (95% CI 1.37 to 1.62); and class IV (n = 898), HR 2.80 (95% CI 2.53 to 3.10). Unexpectedly, in a landmark analysis excluding deaths <30 days after admission, patients in Killip class IV had lower adjusted long-term mortality than those in class III. The adjusted HR for 12-year mortality comparing Killip class IV with Killip class III in patients <60 years of age was 1.71 (95% CI 1.33 to 2.19, p <0.001) and in patients >60 years of age was 2.30 (95% CI 2.07 to 2.56, p <0.001). In conclusion, on the basis of simple clinical features, the Killip classification robustly predicted 12-year mortality after AMI. The heterogeneity in early versus late risk in patients with Killip class IV heart failure underscores the importance of appropriate early treatment in cardiogenic shock.

An efficient certificateless blind signature scheme without bilinear pairing.

Recently, the certificateless public key cryptography (CLPKC) has been studied widely since it could solve both of the certificate management problem in traditional public key cryptography (TPKC) and the key escrow problem in the identity-based public key cryptography (ID-based PKC). To satisfy requirements of different applications, many certificateless blind signature (CLBS) schemes using bilinear pairing for the CLPKC setting have been proposed. However, the bilinear pairing operation is very complicated. Therefore, the performance of those CLBS schemes is not very satisfactory. To solve the problem, we propose an efficient CLBS scheme without bilinear pairing. Performance analysis shows that the proposed scheme could reduce costs of computation and storage. Security analysis shows the proposed scheme is provably secure against both of two types of adversaries.